Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.

BACKGROUND:The angle of screw placement in anterior cervical discectomy and fusion plays a crucial role in determining the stability of the internal fixation system. OBJECTIVE:To predict the impact of different screw placement angles on the stress experienced by the internal fixation system in anterior cervical discectomy and fusion utilizing finite element analysis,with the ultimate goal of identifying the optimal screw placement angle. METHODS:A three-dimensional reconstruction method was employed to establish a mechanical model of the cervical spine,enabling the simulation of three distinct working conditions:scoliosis,uprightness,and forward flexion.In SolidWorks 2017,the anterior cervical plate and screw models were built according to different placement angles of the screws,with a as the inward offset,b as the ideal position,c as the outward offset,d as the downward offset,and e as the upward offset.The stress distribution of internal fixation system at different screw placement angles was observed,and the stress and displacement were recorded. RESULTS AND CONCLUSION:(1)By constructing a finite element model of the entire cervical spine and incorporating an anterior titanium plate,it was found that the biomechanical changes in the spine did not significantly differ based on the various angles of screw insertion on the titanium plate under the same working conditions.(2)However,microscopic analysis revealed that the outward offset(c)screw position exhibited the most effective resistance against side bending,while the downward offset(d)screw demonstrated optimal load-bearing capacity in the upright condition.Additionally,the outward deviation(c)screw displayed superior anti-bending effects in the reverse buckling condition.(3)The fixation effect of the internal fixation device remained relatively stable across different motion conditions.Although there was a 10％variation in the internal fixation effect under the three working conditions when the screw was placed inward,outward,downward,or upward,the displacement changes were minimal.These findings suggest that the requirements of load bearing,bending resistance,and flexion resistance could be simultaneously met without a specific optimal screw location in clinical practice.(4)The placement direction of titanium plate screw in anterior cervical disc-resection and fusion has little effect on the mechanical stability of the cervical spine.The screw angles in different directions have little influence on the stability of the internal fixation device in the lateral,upright,and forward flexion movements of the cervical spine.There is no need to pursue the direction of screw placement in clinical operations.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

Objective To observe the efficacy of gray-scale ultrasound-based radiomics for differentiating peripheral pulmonary adenocarcinoma and squamous cell carcinoma.Methods Data of 88 patients with single peripheral lung adenocarcinoma and 58 patients with single peripheral lung squamous cell carcinoma proved pathologically with puncture biopsy and clearly visualized with lung ultrasound were retrospectively analyzed.The patients were divided into training set(n=103)and test set(n=43)at the ratio of 7:3.Based on gray-scale ultrasound of training set,radiomics features associated with differential diagnosis of peripheral lung adenocarcinoma and lung squamous cell carcinoma were extracted and screened.Using 4 different classifiers,including support vector machine(SVM),linear discriminant analysis(LDA),logistic regression(LR)and the least absolute shrinkage and selection operator combined with logistic regression(LASSO-LR),4 corresponding radiomics models were obtained,and the relative best models were selected according to their performances under 10-fold cross validation.The receiver operating characteristic curves were drawn,the areas under the curve(AUC)were calculated to evaluate the differentiating efficacy of each model,and DeLong test was used for the comparison.The differentiating accuracy of models were obtained under the best cutoff value with the maximum Youden index.Results The AUC of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous carcinoma in test set was 0.864,0.867,0.880 and 0.844,respectively,and no significant difference was found among 4 models(all P＞0.05).Under the best cutoff value of each model,the corresponding accuracy of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous cell carcinoma was 86.05％,83.72％,88.37％and 86.05％,respectively.Conclusion Radiomics models based on gray-scale ultrasound could be used to differentiate peripheral lung adenocarcinoma and lung squamous cell carcinoma.

Objective:To investigate the clinical characteristics of psoriasis and status quo of medical care for patients in county areas of China.Methods:This study was a cross-sectional investigation. Based on the “Qianxian Wuyin” Project (a national project for upgrating ability for psoriasis care at county level), an online questionnaire survey was conducted in the dermatology departments of 459 county hospitals in 404 pilot administrative counties across China from February to June 2023. The questionnaire included demographic information of patients (gender, ethnicity, age, place of residence, education, marital status), and clinical characteristics of psoriasis (disease course, type, comorbidities, body surface area (BSA) and previous treatment. The Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were applied for assessing the quality of life and disease severity, and completed by patients or guardian and doctors, respectively.Results:A total of 16 935 patients completed the questionnaire. The age of patients was 1-102(44.17±11.58)years, and 71.0% (12 036/16 935) were 30-59 years old. The ratio of male to female was 2.21∶1; 24.3%(4 117/16 935) of patients had high school education; there were 9 940 patients(58.7%) with previous or current smoking and/or alcohol use; 42.8%(7 218/16 855) of patients had a disease course of 1-5 years. There were 15 630 patients(92.3%) with DLQI≥10, 8 346 patients(49.7%) with PASI≥10, 15 017 patients(89.2%) with BSA≥10%. The plaque type was the most common disease type ( n=14 965, 88.7%), and spotting type ranked the second ( n=1 141, 6.8%). The most common initial site was the trunk ( n=12 309, 72.9%). Among the comorbidities, hypertension was the most common one ( n=1 681, 10.0%). There were 7 650 reports of treatment response to conventional topical drug therapy and 3 112 reports of treatment response to systemic drug therapy, with 6 269 (81.9%) and 2 493 (80.1%) reporting poor or no response, respectively. Conclusions:The survey shows that in the county areas of China, the majority of psoriasis patients are severe patients with short course of disease, plaque type is the most common type, and hypertension is the most common comorbidity; and the conventional treatment is less effective for most patients.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

In order to further standardize the diagnosis and treatment of atopic dermatitis by health-care professionals, as well as to enhance the awareness of atopic dermatitis among patients and promote doctor-patient communication, Chinese Society of Dermatology and China Dermatologist Association jointly initiated the development of guidelines on the diagnosis and treatment of atopic dermatitis (specialist version, general practitioner version and patient version). The development working group had planned the development process of the 3 versions of guidelines with reference to relevant development manuals and methodological articles. It is also intended to expound the details of registration, working group establishment, clinical question collection, evidence search and grading, recommendation formation and consensus through this protocol, aiming to enhance the transparency of guideline development.

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI), and to clarify the critical role and regulating mechanism of transient receptor potential canonical (TRPC) 6/poly adenosine-diphosphate-ribose polymerase (PARP) 1 signaling pathway during this process. Methods The hucMSC-Exo was extracted by ultracentrifugation, and identified by transmission electron microscope (TEM), nanoparticle tracing analysis and Western blot. SD rats were randomly divided into the sham operation group (group S), sham operation+TRPC6 inhibitor SKF96365 group (group SS), renal IRI group (group IRI), exosome treatment group (group EXO) and exosome +TRPC6 inhibitor SKF96365 group (group ES), with 6 rats in each group. Serum creatinine and blood urea nitrogen levels were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin (HE) staining and Paller score was calculated. The expression levels of key molecules of necroptosis in rat renal tissues, including receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL), TRPC6 and PARP1, were detected by Western blot. Results Typical saucer-like structure was observed under TEM. Nanoparticle tracing analysis showed that the average diameter of the extracted substance was 125.9 nm. Western blot revealed that the surface markers of CD9, CD63 and CD81 were positively expressed, confirmed that the extracted substance was exosome. Compared with group S, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was worsened, Paller score was elevated, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group IRI (all P < 0.05). Compared with group IRI, the serum creatinine and blood urea nitrogen levels were down-regulated, the pathological damage of renal tissues was mitigated, Paller score was decreased, the relative expression levels of TRPC6 and PARP1 proteins were up-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were down-regulated in group EXO (all P < 0.05). Compared with group EXO, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was aggravated, Paller score was increased, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group ES (all P < 0.05). Conclusions hucMSC-Exo may alleviate the necroptosis induced by renal IRI in rat models, which is related to the activation of TRPC6/PARP1 signaling pathway.

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca²⁺ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca²⁺ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

The metastasis of renal cell carcinoma to the ureter is a rare phenomenon, and synchronal detection of metastasis to the contralateral ureter is a rarer phenomenon. A 62-year-old male patient with painless hematuria was examined and detected a renal cell carcinoma on the right kidney and bleeding from the left ureter. Ureteroscopy revealed a tumor in the left upper ureter, and biopsy suggested clear cell carcinoma. Laparoscopic radical nephrectomy was performed to resect the right renal cell carcinoma, and the pathology revealed a clear cell carcinoma, with Fuhrman nuclear grade 2 class. The ureteral tumor was resected 3 months later and the pathology revealed renal clear cell carcinoma. Sunitinib was used for 37 months, and there was no tumor recurrence or metastasis so far.